Vexing questions in the field of genomic biomarkers are: How do we build the evidence to support their clinical use? And what is their clinical value? The objective of this proposal is to develop an innovative framework for clinical effectiveness research (CER) for cancer pharmacogenomics. Specifically we have coordinated expertise from three existing state-of-the-art and unique entities at Duke - the Duke Institute for Genome Sciences &Policy Cancer Pharmacogenomic Biomarkers Program (IGSP-CPBP), the IGSP Clinical Genomics Studies Unit (IGSP-CGSU), and the Duke Health Services, Effectiveness and Outcomes Research Program (DHSEORP) - into a single entity, the Duke Center for Clinical Effectiveness of Cancer Pharmacogenomics. This new Center will be part of a network wholly focused CER for genomic and personalized medicine in cancer. The specific aims are: Aim 1 - To develop a comprehensive registry of biological samples and health and economic data to support evidence generation and clinical effectiveness research for evaluating cancer pharmacogenomic markers in lung and breast cancer. This opportunity leverages the established infrastructure to carry out genome-guided clinical trials and, in the context of this proposal, to develop a prospective cancer population registry for patients receiving care/therapies for lung and breast cancers at Duke. This registry will bank tissue, blood, and collect detailed phenotypic and outcome, as well as health system utilization data from the electronic health records and Duke Clinical Data Repository. The deliverable from the registry will be the data and evidence to establish a 'proof of concept'for the use of RNA expression data from tumors to guide the use of approved chemotherapies. Aim 2 - To develop guidelines for the systematic evaluation and integration of genomic and clinical data, using literature databases, a longitudinal registry of breast and lung cancers and ongoing prospective genomeguided trials. A multidisciplinary CER team and network will develop an iterative process for systematic data reviews (based on EGAPP) from ongoing genomic guided clinical trials at Duke, the registry in Aim 1, and the literature. Completion of the aims will result in: a) A CER program that enables the identification of the most effective health care options for the treatment of lung and breast cancers;b) A program that links data from public databases and the Duke Health System;c) Specific studies in breast and lung cancer that support the development of 'personalized medicine'based on genomic information;and, d) A process to ensure that information gained through CER is disseminated for adoption into clinical practice and decision making. PUBLIC HEALTH RELEVANCE: Each year, over 700,000 cancer treatment decisions are made in the United States. Too often there is little or no guidance for clinicians to base their selection of available treatments. We will evaluate novel predictive gene expression biomarkers that offer an opportunity to direct treatments to those most likely to respond, reduce unnecessary treatment toxicity, thus improving clinical outcome and personalizing cancer treatment.